To provide an initial step toward the understanding of the functional relationship between the onc genes of transforming retroviruses and their cellular prototypes, structural comparisons at the nucleic acid and protein levels have been carried out. We have determined the complete nucleotide sequence of the chicken and human c-myc genese and compared them to two members of the myc facmily of transforming retroviruses: MC29 and OK10. Although a close relationship between the viral and cellular myc genes has been found, these genes are not isogenic. The myc-related genes of MC29, MH2, and OK10, and the myb-related genes of AMV and E26 are genetic hybrids with sequences derived from viral structural genes and parts of essential cellular proto-onc genes. The cellular genes contain additional 5' sequences. The substitution of viral genes for parts of the normal cellular genes may be the most significant difference between these genes, perhaps eliciting functional differences between their gene products. We have initiated studies of the cellular ets gene to determin whether this pattern of a truncated normal gene in the transforming retorvirus can be extended to other onc genes. The cellular gene transcript is considerably large than the amount of DNA transduced by the virus. We have determined that the mammalian homologues of v-ets consist of two distint domains located on different chromosomes. Using chromosome-specific probes, we have shown that both loci (ets-1 and ets-2) are transcriptionally active, producing mRNA species. The sequences homologous to ets-1 and ets-2 are colinear in chicken prot-ets and have possibly become separate and functionally distinct since before the evolutionary divergence of mammalia.